ClinVar Genomic variation as it relates to human health
NM_000492.4(CFTR):c.3107C>A (p.Thr1036Asn)
The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.
Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_000492.4(CFTR):c.3107C>A (p.Thr1036Asn)
Variation ID: 53652 Accession: VCV000053652.25
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 7q31.2 7: 117610637 (GRCh38) [ NCBI UCSC ] 7: 117250691 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
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First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.
Last submission Help The date of the most recent submission for each type of classification for this variant.
Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline Jan 25, 2018 May 1, 2024 Mar 11, 2019 - HGVS
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Nucleotide Protein Molecular
consequenceNM_000492.4:c.3107C>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000483.3:p.Thr1036Asn missense NC_000007.14:g.117610637C>A NC_000007.13:g.117250691C>A NG_016465.4:g.149854C>A NG_056128.2:g.3691C>A LRG_663:g.149854C>A LRG_663t1:c.3107C>A LRG_663p1:p.Thr1036Asn - Protein change
- T1036N
- Other names
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- Canonical SPDI
- NC_000007.14:117610636:C:A
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Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
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Global minor allele
frequency (GMAF) HelpThe global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.
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Allele frequency
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The frequency of the allele represented by this VCV record.
Trans-Omics for Precision Medicine (TOPMed) 0.00001
The Genome Aggregation Database (gnomAD), exomes 0.00000
The Genome Aggregation Database (gnomAD) 0.00001
Genes
Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
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Links to Variation Viewer, a genome browser to view variation data from NCBI databases. |
Related variants | ||
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HI score
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The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
TS score
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The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
Within gene
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The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants. |
All
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The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene. |
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CFTR | - | - |
GRCh38 GRCh37 |
3704 | 5025 | |
LOC111674472 | - | - | - | GRCh38 | - | 387 |
Conditions - Germline
Condition
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The condition for this variant-condition (RCV) record in ClinVar. |
Classification
Help
The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions) |
Review status
Help
The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. |
Last evaluated
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The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
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The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page. |
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Pathogenic (6) |
reviewed by expert panel
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Mar 11, 2019 | RCV000577654.13 | |
Likely pathogenic (1) |
criteria provided, single submitter
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Feb 21, 2019 | RCV000781270.10 | |
Pathogenic (1) |
criteria provided, single submitter
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- | RCV001004291.2 | |
Likely pathogenic (1) |
criteria provided, single submitter
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Sep 2, 2021 | RCV002254276.5 |
Submissions - Germline
Classification
Help
The submitted germline classification for each SCV record. (Last evaluated) |
Review status
Help
Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria) |
Condition
Help
The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant. |
Submitter
Help
The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar. |
More information
Help
This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter. |
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Pathogenic
(Mar 11, 2019)
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reviewed by expert panel
Method: research
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Cystic fibrosis
Affected status: yes
Allele origin:
germline
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CFTR2
Accession: SCV000924217.1
First in ClinVar: Jun 17, 2019 Last updated: Jun 17, 2019 |
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Pathogenic
(-)
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criteria provided, single submitter
Method: clinical testing
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Congenital bilateral aplasia of vas deferens from CFTR mutation
Cystic fibrosis
Affected status: unknown
Allele origin:
germline
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Baylor Genetics
Accession: SCV001163167.1
First in ClinVar: Feb 29, 2020 Last updated: Feb 29, 2020 |
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Likely pathogenic
(Sep 02, 2021)
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criteria provided, single submitter
Method: clinical testing
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Not provided
Affected status: unknown
Allele origin:
germline
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Mayo Clinic Laboratories, Mayo Clinic
Accession: SCV002525779.1
First in ClinVar: Jun 11, 2022 Last updated: Jun 11, 2022 |
Comment:
PM2, PM3_strong
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Likely pathogenic
(Sep 05, 2022)
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criteria provided, single submitter
Method: curation
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Cystic fibrosis
Affected status: yes
Allele origin:
unknown
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Institute of Human Genetics, University of Leipzig Medical Center
Accession: SCV002574031.1
First in ClinVar: Sep 24, 2022 Last updated: Sep 24, 2022 |
Comment:
This variant was identified in 1 patient with a clinically confirmed diagnosis of cystic fibrosis. The variant was classified in the context of a project … (more)
This variant was identified in 1 patient with a clinically confirmed diagnosis of cystic fibrosis. The variant was classified in the context of a project re-classifying variants in the German Cystic Fibrosis Registry (Muko.e.V.). Link: https://www.muko.info/angebote/qualitaetsmanagement/register/cf-einrichtungen/mukoweb. Criteria applied: PM2_SUP, PM3_STR, PM5, PP3 (less)
Number of individuals with the variant: 1
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Pathogenic
(Oct 25, 2022)
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criteria provided, single submitter
Method: clinical testing
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Cystic fibrosis
Affected status: unknown
Allele origin:
germline
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Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV000919182.2
First in ClinVar: Jun 02, 2019 Last updated: Nov 19, 2022 |
Comment:
Variant summary: CFTR c.3107C>A (p.Thr1036Asn) results in a non-conservative amino acid change located in the ABC transporter type 1, transmembrane domain of the encoded protein … (more)
Variant summary: CFTR c.3107C>A (p.Thr1036Asn) results in a non-conservative amino acid change located in the ABC transporter type 1, transmembrane domain of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 4e-06 in 250950 control chromosomes. c.3107C>A has been reported in the literature as a biallelic compound heterozygous or homozygous genotype in multiple individuals affected with Cystic Fibrosis (example, Giusti_2007, McGinniss_2005, Salinas_2016). These data indicate that the variant is very likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Four clinical diagnostic laboratories and an expert panel (CFTR2) have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All submitters classified the variant as pathogenic/likely pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic. (less)
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Likely pathogenic
(Oct 15, 2021)
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criteria provided, single submitter
Method: clinical testing
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Cystic fibrosis
Affected status: unknown
Allele origin:
germline
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Ambry Genetics
Accession: SCV002605991.2
First in ClinVar: Nov 29, 2022 Last updated: May 01, 2024 |
Comment:
The p.T1036N variant (also known as c.3107C>A), located in coding exon 19 of the CFTR gene, results from a C to A substitution at nucleotide … (more)
The p.T1036N variant (also known as c.3107C>A), located in coding exon 19 of the CFTR gene, results from a C to A substitution at nucleotide position 3107. The threonine at codon 1036 is replaced by asparagine, an amino acid with similar properties. This variant was reported in a homozygous individual with a classic presentation of cystic fibrosis (McGinniss MJ et al. Hum Genet, 2005 Dec;118:331-8). This variant was also reported in trans with p.F508del mutation in an individual with classic cystic fibrosis (Petrova NV et al. Genes (Basel), 2020 05;11:). Additionally, this variant has been reported in multiple individuals with an elevated sweat chloride level in The Clinical and Functional TRanslation of CFTR (CFTR2) database (available at http://cftr2.org. Accessed 10/14/2021). This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Based on the majority of available evidence to date, this variant is likely to be pathogenic. (less)
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Likely pathogenic
(Feb 21, 2019)
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criteria provided, single submitter
Method: clinical testing
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not specified
Affected status: unknown
Allele origin:
germline
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ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories
Accession: SCV001160337.1
First in ClinVar: Feb 10, 2020 Last updated: Feb 10, 2020 |
Comment:
The CFTR c.3107C>A; p.Thr1036Asn variant (rs397508498) is reported in the literature in individuals affected with either pancreatic-sufficient or pancreatic-insufficient cystic fibrosis (CF) (Chavez-Saldana 2010, McGinniss … (more)
The CFTR c.3107C>A; p.Thr1036Asn variant (rs397508498) is reported in the literature in individuals affected with either pancreatic-sufficient or pancreatic-insufficient cystic fibrosis (CF) (Chavez-Saldana 2010, McGinniss 2005, Salinas 2016). This variant has been identified in affected individuals both in the homozygous state (McGinniss 2005) and in heterozygous individuals with an additional pathogenic variant (Salinas 2016). This variant is found on only two chromosomes in the Genome Aggregation Database, indicating it is not a common polymorphism. The threonine at codon 1036 is highly conserved and computational analyses (SIFT, PolyPhen-2) predict that this variant is deleterious. Additionally, another variant at the same codon (p.Thr1036Ile) has been reported in individuals with CF and is considered pathogenic (Alibakhshi 2008, Sahami 2014). Based on available information, the p.Thr1036Asn variant is considered to be likely pathogenic. References: Alibakhshi R et al. Analysis of the CFTR gene in Iranian cystic fibrosis patients: identification of eight novel mutations. J Cyst Fibros. 2008 Mar;7(2):102-9. Chavez-Saldana M et al. CFTR allelic heterogeneity in Mexican patients with cystic fibrosis: implications for molecular screening. Rev Invest Clin. 2010 Nov-Dec;62(6):546-52. McGinniss MJ et al. Extensive sequencing of the CFTR gene: lessons learned from the first 157 patient samples. Hum Genet. 2005 Dec;118(3-4):331-8. Sahami A et al. Mutation Analysis of Exons 10 and 17a of CFTR Gene in Patients with Cystic Fibrosis in Kermanshah Province, Western Iran. J Reprod Infertil. 2014 Jan;15(1):49-56. Salinas DB et al. Benign and Deleterious Cystic Fibrosis Transmembrane Conductance Regulator Mutations Identified by Sequencing in Positive Cystic Fibrosis Newborn Screen Children from California. PLoS One. 2016 May 23;11(5):e0155624. (less)
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Pathogenic
(Jul 16, 2023)
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criteria provided, single submitter
Method: clinical testing
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Cystic fibrosis
Affected status: unknown
Allele origin:
germline
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Invitae
Accession: SCV002135510.3
First in ClinVar: Mar 28, 2022 Last updated: Feb 14, 2024 |
Comment:
Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) … (more)
Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on CFTR protein function. This variant disrupts the p.Thr1036 amino acid residue in CFTR. Other variant(s) that disrupt this residue have been observed in individuals with CFTR-related conditions (PMID: 17662673), which suggests that this may be a clinically significant amino acid residue. For these reasons, this variant has been classified as Pathogenic. This sequence change replaces threonine, which is neutral and polar, with asparagine, which is neutral and polar, at codon 1036 of the CFTR protein (p.Thr1036Asn). This variant is present in population databases (rs397508498, gnomAD 0.004%). This missense change has been observed in individual(s) with cystic fibrosis (PMID: 16189704, 27214204, 32429104). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 53652). (less)
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not provided
(-)
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no classification provided
Method: literature only
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CFTR-related disorders
Affected status: yes
Allele origin:
germline
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ClinVar Staff, National Center for Biotechnology Information (NCBI)
Accession: SCV000679029.1
First in ClinVar: Jan 25, 2018 Last updated: Jan 25, 2018 |
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Germline Functional Evidence
There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar. |
Citations for germline classification of this variant
HelpTitle | Author | Journal | Year | Link |
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Analysis of CFTR Mutation Spectrum in Ethnic Russian Cystic Fibrosis Patients. | Petrova NV | Genes | 2020 | PMID: 32429104 |
The CFTR variant profile of Hispanic patients with cystic fibrosis: Impact on access to effective screening, diagnosis, and personalized medicine. | Januska MN | Journal of genetic counseling | 2020 | PMID: 32227567 |
Benign and Deleterious Cystic Fibrosis Transmembrane Conductance Regulator Mutations Identified by Sequencing in Positive Cystic Fibrosis Newborn Screen Children from California. | Salinas DB | PloS one | 2016 | PMID: 27214204 |
Newborn Screening for Cystic Fibrosis in California. | Kharrazi M | Pediatrics | 2015 | PMID: 26574590 |
[Genotype-phenotype correlation in a sample of Mexican patients with cystic fibrosis]. | Yokoyama E | Revista de investigacion clinica; organo del Hospital de Enfermedades de la Nutricion | 2013 | PMID: 24687356 |
CFTR allelic heterogeneity in Mexican patients with cystic fibrosis: implications for molecular screening. | Chávez-Saldaña M | Revista de investigacion clinica; organo del Hospital de Enfermedades de la Nutricion | 2010 | PMID: 21416780 |
Analysis of the CFTR gene in Iranian cystic fibrosis patients: identification of eight novel mutations. | Alibakhshi R | Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society | 2008 | PMID: 17662673 |
New York State cystic fibrosis consortium: the first 2.5 years of experience with cystic fibrosis newborn screening in an ethnically diverse population. | Giusti R | Pediatrics | 2007 | PMID: 17272608 |
Extensive sequencing of the CFTR gene: lessons learned from the first 157 patient samples. | McGinniss MJ | Human genetics | 2005 | PMID: 16189704 |
https://cftr2.org | - | - | - | - |
Text-mined citations for rs397508498 ...
HelpRecord last updated May 08, 2024
This date represents the last time this VCV record was updated. The update may be due to an update to one of the included submitted records (SCVs), or due to an update that ClinVar made to the variant such as adding HGVS expressions or a rs number. So this date may be different from the date of the “most recent submission” reported at the top of this page.